Preparation of 2-acylpyrroles from 2-acylfurans



Patented Oct. 13, 1953 UNITED STATES PATENT OFFICE PREPARATION OF Z-ACYLPYRROLES FROM 2-ACYLFURAN S Andrew P. D'unlop,

Swadesh, Broadview,

Quaker Oats ration of New Jersey N Drawing'. Application Riverside, and Samuel Ill'., assignors to The Company,

Chicago, 111., a corpo- Jllne 22, 1950,

Serial No. 169,773 12 Claims. (Cl. 260-3265);

vention to provide an eflicient process for. thepreparation of Z-acylpyrroles. Another object is to provide a process for the preparation of 2-acy1pyrroles in a direct manner which canbe easily carried out using relatively inexpensive equipment. A very important object is to provide an improved process for producing 2-acylpyrroles by reacting a Z-acylfuran with a nitrogen base. Other objects and advantages of the present invention will become apparent to those skilled in the art as the invention is more fully described. I I

Broadly stated, the present invention provides an improved process for the production of 2-acylpyrroles which comprises heating a Z-acylfuran with a suitable nitrogen base at elevated temperatures. In view of the fact that the particular reactants used may be selected from a large list and since the best operating temperature depends largely upon the specific reactants used, the temperature employed may vary from about" 50 to 250 C. Generally, we prefer to operate within a temperature range of- 80 to 200 C. It is to=be understood, however, that higher or lower temperatures may be used with a-resultant increase or decrease in the reaction. rate in accordance with the general lawof chemical reactions.

The. proportion of reactants, i. e., 2-acy1furan andthe nitrogen base used in our process may be varied over a wide range. Theoretically in our process, one mole of the 2-acylfuran reacts with one mole of the nitrogen base to form a ketimine, or Schilfs base, and with an additional mole of nitrogen base to form a pyrrole; in accordance with the following equations:

' In practice, however, we

Wherein R. may be hydrogen, alkyl, aryl,v R. maybe,

aralkyl, or a heterocyclic radical. alkyl, aryl, aralkyl may be" hydrogen, radical.

The ketimine of the to the Z-acylpyrrole:

Thus, two males of nitrogen: base are: required.

prefer to employ an excess' of the nitrogen base over thez'2.-acylfuran.

Asia general rule, an added solvent'is not necesor a heterocyclic' radical. R alkyl, aralkyl or a heterocyclie pyrrole is easily hydrolyzed 2-acylpyrrole with difierent solvents. ample, when the nitrogen base isammonia, a competing reaction may occur if ethanol is used as the solvent and ahydroxypyridine maybe formed in addition to the z-acylpyrrole. mixed alcohol-water medium, used, the competing reaction trative. examples will be given in which parts by weight bear the same relation to parts by volume as dov grams to cubic centimeters.

EXAll/IPL13} 1 Preparation of Z-acetylpyrrole To 30 parts by weight of 2-acetylfuran was added 97 parts by weight'of anhydrous ammonia dissolved in 800 parts by volume of ethanol. After heating the solution for about twenty hours at to C. in an autoclave the solution was concentrated to 50 parts by volume by distillation under reduced pressure. The residue, upon cooling, yielded 2.9 parts by weight (10 per cent of theory) of crystalline 2-methyl-3-hydroxypyridine as a precipitate which had a melting point of 168.3168.5 C. The filtrate, upon distillation under reduced pressure, yielded 11.1 parts by weight of Z-acetylpyrrole M. P. 90.0-

90.5" C. which represented a 38 per cent yield of theory.

Analysis H N OIH'IONZ Theory 66. 1 6. 43 12. 84 Found 65.84 6.55 use EXAMPLE 2 Preparation of Z-acetylpyrrole Thirty parts by weight of Z-acetyliuran was added to 50 parts by volume of liquid ammonia which resulted in a rather vigorous reaction with the formation of acetylfuran ketimine. After the reaction had subsided, 100 parts by volume of liquid ammonia additional was added, the resulting solution heated for 16 hours at 100-1l0 C. in an autoclave and then the excess ammonia removed by distillation. The residue was dissolved in ether, filtered, ether removed by evaporation and the residue distilled under vacuum. 2.6 parts by weight of 2-acetylpyrro1e boiling range 84-8'l C. at 2 mm. was obtained which represented a yield of 8.8 per cent of theory.

EXAMPLE 3 Preparation of I-n-DutyZ-Z-acetylpyrrole To 30 parts by weight of 2-acetylfuran were added 60 parts by weight of n-butylamine and 350 parts by volume of ethanol. After heating the solution for about 7 /2 hours at 125130 C. in the autoclave, the ethanol and excess n-butylamine were removed by distillation and upon under reduced pressure by weight (17 per cent of theory) of 1-n-butyl-2-acetylpyrrole was obtained. The product had a boiling range of 72-74 C. at about 1 mm. Its 2,4-dinitrophenylhydrazone derivative melted at 147.0147.5 C. By further distillation under reduced pressure 9.9 grams of a higher boiling point range (115- 135 C. at 1 mm.) was obtained which probably contained the butyl ketimine of 1-n-butyl-2- acetylpyrrole.

Analysis 0 H N C HnON:

Theory 72.7 9.08 8.48 165 Found 72.58 9.37 8.01 163 EXAMPLE 4 Preparation of l-n-butyl-Z-acetylpyrrole 2-Acetylfuran (30 parts by weight) and nbutylamine (60 parts by weight) were autoclaved for 18 hours at a temperature of 150-155 C. cooled and then after removing the excess nbutylamine the product was distilled under a vacuum. A yield of 16.3 parts by weight (36 per cent of theory) of 1-n-butyl-2-acetylpyrrole which had a boiling range of 72 to 74 C. at about 1 mm. was obtained.

EXAMPLE 5 Preparation of 1-n-batyl-2-propionylpyrrole To 30 parts by weight of 2-propionylfuran was added 53 parts by weight of n-butylamine and 300 parts by volume of methanol. After heating the foregoing solution for about 1'7 hours at to C. in an autoclave, the alcohol and excess n-butylamine were removed by distillation under reduced pressure. Upon continuing the distillation of 1 mm., 26.6 parts by weight of distillate was collected and the distillate so collected was refluxed for 15 minutes with 20 parts by volume of 2 normal sulfuric acid. After cooling, the mixture was extracted with ether in 5 increments, the ether layers combined, dried over anhydrous sodium sulfate and the ether removed by distillation. From the extract, 4.4 parts by weight of 1-n-butyl-2-propionylpyrro1e having a boiling range of 82 to 84C. at 1.5 mm. was obtained, equivalent to a yield of 12 per cent of theory.

Analysis C H N CiiHUONi Theory 73. 7 9. 56 7. 82 Found 72. 51 9. 66 7. 58

EXAMPLE 6 Preparation of 1-methyl-3,4-dihydropyrrolo [1,2-a] pyrazine Analysis 0 H N CaHmNrt Theory 71. 64 7. 46 20. 80 Found 71. 60 7. 64 21. 00

EXAMPLE '1 Preparation of 1-n-dodecyl-2-acetylpyrrole and 1-n-tetradecyl-2-acetylpyrrole ing at 149 to 159 C. at 1 mm. The 2,4-dinitrophenylhydrazone derivative had a M. P. of 860 to 865 C. and showed: 7

Analysis 0 H N OMHNOANII Theor 63. 02 7. 66 15. 32 Penn 53.11 1.15 15. a)

4.2 parts by weight of an additional fraction (1-n-tetradecyl-2-acetylpyrrole) having a boiling range of 168 to 171 C. at 1 mm. was obtained.

gamers Its 2 ,4 dinitrophenylhydrazone had a M. P. of 79.5 to 80.0? C. and showed:

To 70 parts by weight of 5-methyl-2-acetylfuran were added 100 parts by weight of nbutylamine and 100 parts by volume of methanol. After heating the foregoing solution for about 21 hours at about 180 C. in an autoclave, the alcohol and excess n-butylamine were removed by distillation under reduced pressure. Upon continuing the distillation at a pressure of about 0.7 mm., 23.7 parts by weight of crude 1-n-butyl-5- methyl-2-acetylpyrrole boiling over a range of 80 to 116 C. was obtained. Redistillation gave 14.2 g. (12% yield) of the pure compound boiling at 94.5 to 950 C. at 1.6 mm. A 2,4-dinitrophenylhydrazone derivative melted at 151.8 to 152.6 C. and showed:

Although the present invention has been described in conjunction with preferred embodiments, it is to be understood that modifications and variations may be resorted to without departing from the spirit and scope of the invention, as those skilled in the art will readily understand. As for example, in addition to the acylfurans enumerated in the specific example, higher members of the homologous series such as butyryl, valeryl, caproyl f-urans, etc., may be treated with nitrogen bases in a similar manner to produce the corresponding :pyrroles. Such variations and modifications are considered to be within the purview and scope of the appended claims.

We claim:

1. A process for role which comprises the general formula:

UE-R

in which R. is an alkyl radical containing not more than 2 carbon atoms with a nitrogen base selected from the class consisting of ammonia and saturated alkyl primary amines at a temperature of 50 to 250 C. wherein the molar ratio of the nitrogen base to the acylfuran is at least 2 to 1.

2. A process for the role which comprises the general formula:

UE-R

in which R is an alkyl radical containing not more than 2 carbon atoms which a nitrogen base [the production of a 2-acylpyrreacting a 2-acylfuran of production of a 2-acylpyrreacting a 2-acy1furan of selected from the class consisting of ammonia;v

and saturated alkyl primary amines. at a temperature of to 200 ratio of :the nitrogen base to the acylfuran is at least 2 to 1.

3. A process-for the role which comprises the general formula:

in which R is an alkyl radical containing not more than 2 carbon atoms with ammonia at a temperature of 80 to 200 C. wherein the molar ratio of the ammonia :to the acylfuran is at least 2 to 1.

5. A process for the production of 2-acetylpyrrole which comprises reacting 2-acetylfuran with ammonia at a temperature of 50 to 250 C. wherein the molar ratio of the ammonia :to the acetylfuran is at least 2 to 1.

6. A process for the production of 2-acetylpyrrole which comprises reacting 2-acetylfuran with ammonia at a temperature of 80 to 200 C. wherein .the molar ratio of ammonia to the acetylfuran is at least 2 to 1.

7. A process for the production of a 2-acetylpyrrole which comprises reacting 2-acetylfuran with a nitrogen base selected from the class consisting of ammonia and saturated alkyl primary amines at a temperature of 50 to 250 C. wherein the production of a 2-acylpyrreacting a 2-acylfuran of molar ratio of the nitrogen base to the acetylfuran is at least 2 to 1.

8. A process for the production of a 2-acetylpyrrole which comprises reacting 2-acetylfuran with a nitrogen base selected from the class consisting of ammonia and saturated alkyl primary amines at a temperature of 80 to 200 C. wherein the molar ratio of the nitrogen base to the acetylfuran is at least 2 to 1.

9. A process for :the production of a 1-butyl-2- acylpyrrole which comprises reacting a 2-acylfuran of the general formula:

in which R is an alkyl radical containing not more than 2 carbon atoms with butylamine at a temperature of 50 to 250 C. wherein the molar ratio of the butylamine $0 the acylfuran is at least 2 to 1.

10. A process for the production of a 1-butyl-2- acylpyrrole which comprises reacting a 2-acylfuran of the general formula:

in which R is an alkyl radical containing not more than 2 carbon atoms with butylamine at a tem- C. wherein the molar 7 perature of 80 to 200 C. wherein the molar ratio of the butylamine to the acyli-uran is at least 2 to 1.

11. A process for the production of 1-buty1-2- acetylpyrrole which comprises reacting z-acetylturan with butylamlne at a temperature of 50 to 250 C. wherein the molar ratio of the butylamine to the acetylturan is at least 2 to 1.

12. A process for the production or 1-buty1-2- acetylpyrrole which comprises reacting 2-acetylturan with butylamine at a temperature of 80 to 200 C. wherein the molar ratio or the butylamine to the acetylfuran is at least 2 to 1.

ANDREW P. DUNIDP. SAMUEL SWADESH.

References Cited in the flle 0! this patent UNITED STATES PATENT Name Date McNally Aug. 29, 1939 Knorr et al.: Berichte 45, pp. 2631-5, abstracted in Chem. Abst., vol. '1, p. 348. 

1. A PROCESS FOR THE PRODUCTION OF A 2-ACYLPYRROLE WHICH COMPRISES REACTING A 2-ACYLFURAN ON THE GENERAL FORMULA: 